Prevalence of Hypertension, Diabetes Mellitus, and Dyslipidemia in Patients with Chronic Obstructive Pulmonary Disease

Recent studies have shown that chronic obstructive pulmonary disease (COPD) causes various extrapulmonary comorbidities. In addition, cardiovascular disease, the pathogenesis of which involves atherosclerosis, has been emphasized as a cause of mortality in patients with COPD. In the present study, we investigated the presence of classical risk factors for atherosclerosis in 183 patients with COPD. The prevalence of comorbidities (hypertension, diabetes mellitus [DM], and dyslipidemia) was investigated and compared with that in a general population. In patients with COPD, the prevalence of hypertension, DM, and dyslipidemia was 43.2%, 15.8%, and 25.7%, respectively, with the prevalence of DM and dyslipidemia significantly higher in patients than in the general population. Furthermore, there were significant differences in the prevalence of the three disorders in patients with COPD. For example, the prevalence of hypertension was significantly higher than that of diabetes mellitus in patients aged 60-69 years and higher than the prevalence of DM and dyslipidemia in patients aged ≥ 70 years. Regardless of age, hypertension was noted in the greatest number of patients. In conclusion, a high proportion of patients with COPD were found to have the classical risk factors for atherosclerosis. In particular, the prevalence of DM and dyslipidemia was significantly higher in COPD patients than in the general population

Improvement in Frailty in a Patient With Severe Chronic Obstructive Pulmonary Disease After Ninjin'yoeito Therapy: A Case Report

Frailty is a poor prognostic factor in patients with chronic obstructive pulmonary disease (COPD). Although various studies have assessed the effects of conventional treatment with bronchodilators, nutritional support, and pulmonary rehabilitation for frailty in patients with COPD, none have addressed the effects of traditional Japanese medicine (Kampo medicine). Herein, we report the successful management of frailty using Ninjin'yoeito therapy in a 76-year-old patient with COPD. Despite being prescribed multiple bronchodilators, nutritional supplement therapy, patient education, and pulmonary rehabilitation, the patient exhibited unintentional weight loss, low energy, and low physical activity. Ninjin'yoeito was prescribed and these subjective symptoms began to improve 1 month after treatment initiation. In 6 months, the patient reported no frailty, had increased muscle mass, and had achieved an almost normal healthy state. Ninjin'yoeito has been associated with both physical effects, such as improvement in overall physical strength and appetite, and reduction in fatigue, and psychological effects, such as greater motivation and reduction of depression and anxiety symptoms. Physicians have usually treated COPD primarily with organ-specific treatments, such as bronchodilators; however, addressing both the physiological and psychological vulnerability has been difficult. This case report illustrates the potential usefulness of Ninjin'yoeito treatment for frailty in patients with COPD

Cross-talk between TLR3 and TNF-α or IFN-γ Signaling in Induction of CXCL8/IL-8 and CXCL10/IP-10 Expression in Airway Epithelial Cells

CXCL8/IL-8 is a chemoattractant for neutrophils and mast cells, and regulates inflammatory cell recruitment in allergy, infection, and other neutrophil-related diseases. Interferon (IFN) -γ-inducible protein 10 (CXCL10/IP-10) is a chemokine that attracts mononuclear cells, Th1 cells, and natural killer cells. We investigated the levels of CXCL8/IL-8 and CXCL10/IP-10 expression by airway epithelial cells after exposure to the inflammatory cytokines tumor necrosis factor (TNF) -α and IFN-γ, and to poly I:C, a synthetic analog of double-stranded RNA that is a ligand of Toll-like receptor 3 (TLR3). Poly I:C, TNF-α, IFN-γ, and combinations of poly I:C with TNF-α or IFN-γ were used to stimulate the airway epithelial cell line BEAS-2B. Following stimulation, we determined CXCL8/IL-8 and CXCL10/IP-10 mRNA levels by real-time PCR and protein levels by ELISA. Poly I:C treatment upregulated mRNA and protein expression for both CXCL8/IL-8 and CXCL10/IP-10. The addition of TNF-α, but not IFN-γ, to poly I:C further increased the expression of CXCL8/IL-8 mRNA and protein. The addition of either TNF-α or IFN-γ to the poly I:C treatment further increased CXCL10/IP-10 mRNA and protein expression. Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CXCL8/IL-8 and CXCL10/IP-10 in airway epithelial cells. From our results, TNF-α and IFN-γ produce different effects on TLR3 signaling

Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

Association between Catechol-O-Methyltrasferase Val108/158Met Genotype and Prefrontal Hemodynamic Response in Schizophrenia

BACKGROUND:"Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS). METHODOLOGY/PRINCIPAL FINDINGS:Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE:These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging

Effectiveness of Therapeutic Monoclonal Antibodies for Asthma Control in Uncontrolled Eosinophilic Asthma-A Meta-analysis of Randomized Controlled Trials-

The overall efficacy of therapeutic monoclonal antibodies （mAbs） for asthma control in patients with uncontrolled eosinophilic asthma remains to be fully characterized. We conducted a meta-analysis of randomized controlled trials （RCTs） to analyze the efficacies of new therapeutic mAbs, such as anti-interleukin （IL）-13 therapies, anti-IL4/13 therapies, and anti-IL-5 therapies, compared with that of a placebo in patients with uncontrolled asthma. This meta-analysis complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses （PRISMA） guidelines. The primary efficacy outcome was asthma control as assessed by Asthma Control Questionnaire （ACQ） scores. Pooled estimates are presented as standardized mean differences （Std MDs） with 95% confidence intervals （CIs）. Seven RCTs of therapeutic mAbs, including anti-IL-13, anti-IL-4/13, and anti-IL-5, met the criteria for study inclusion. The overall Std MD of changes in the ACQ score was −0.31 （95% CI, −0.45 to −0.17; P＜0.0001）. These results strongly indicate that therapeutic mAbs are effective in controlling asthma in patients with uncontrolled eosinophilic asthma

Anti-interleukin-13, a Monoclonal Antibody, in Uncontrolled Asthma: Systematic Review and Meta-analysis

The overall efficacy and safety of anti-interleukin (IL)-13 therapies remain to be fully characterized. We conducted a meta-analysis of randomized controlled trials (RCTs) on the efficacy and safety of anti-IL-13 therapies compared with placebo in patients with uncontrolled asthma. This meta-analysis complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary efficacy outcome was pulmonary function, and the primary safety outcome was the incidence rate of all adverse events (AAEs). Secondary outcomes included asthma exacerbation, asthma control, and asthma-related quality of life (QoL). Pooled estimates are presented as mean differences (MDs), hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). Five RCTs of anti-IL-13 therapies, including tralokinumab, GSK679586, or lebrikizumab, met the criteria for study inclusion. The overall MD for change in forced expiratory volume in 1 second was 0.08 (95% CI 0.02, 0.15). The RR for the incidence of AAEs compared with placebo was 1.03 (95% CI 0.86, 1.25). The time to first exacerbation improved significantly in the anti-IL-13 compared with placebo group (HR 0.69; 95% CI 0.55, 0.87). Analysis of asthma control and asthma-related QoL revealed significant improvements in the Asthma Control Questionnaire-6 and Asthma Quality of Life Questionnaire scores among anti-IL-13-compared with placebo-treated patients, with MDs of −0.17 (95% CI −0.29, −0.04) and 0.19 (95% CI 0.08, 0.31), respectively. These results strongly indicate that anti-IL-13 therapies are effective and generally well tolerated in patients with uncontrolled asthma

Meta-analysis of Low-versus High-dose Benralizumab in Adults with Uncontrolled Eosinophilic Asthma

The aim of the present study was to assess the non-inferiority of low-dose benralizumab relative to high-dose benralizumab as a treatment option for uncontrolled eosinophilic asthma through a meta-analysis of efficacy and safety in randomized controlled trials (RCTs). PubMed, the Cochrane Library Database, and Scopus were searched to identify relevant articles. Outcome measures were a change in the Asthma Control Questionnaire-6 (ACQ-6) score and the exacerbation rate. In addition, the meta-analysis assessed the incidence of adverse events, injection site reactions, and pyrexia or influenza-like illness. Two RCTs with two doses of benralizumab (20 and 100mg) and a placebo for the treatment of uncontrolled eosinophilic asthma met the criteria and were included in the present study. Non-inferiority of low-dose (20mg) versus high-dose (100mg) benralizumab was shown for the change in ACQ-6 score, exacerbation rate, and the incidence of adverse events, injection site reactions, and pyrexia or influenza-like illness. Although not significant, the incidence of pyrexia or influenza-like illness was lower in patients treated with low-dose benralizumab. These results suggest that low-dose (20mg) benralizumab is effective for symptom control and reduction of exacerbation rate in uncontrolled eosinophilic asthma, with lower treatment costs

On-Demand Inhaled Corticosteroid and Fast-Acting Beta-2 Agonist Combination Therapy Versus Regular Inhaled Corticosteroid Plus Rescue Bronchodilator in Adults with Mild Asthma: A Network Meta-Analysis

The aim of this study was to assess the non-inferiority of on-demand (OD) inhaled corticosteroid (ICS) and fast-acting beta-2 agonist (FABA) combination therapy. Although regular inhalation of low-dose ICS and OD short-acting beta-2 agonist (REG-ICS+OD-SABA) is said to be effective therapy for mild asthma, we investigated whether OD-ICS/FABA is as effective as REG-ICS+OD-SABA. A network meta-analysis of randomized controlled trials was conducted to examine non-inferiority by comparing the efficacy of NON-REG+OD-ICS/FABA with REG-ICS+OD-SABA for mild asthma. We also assessed the superiority of NON-REG+OD-ICS/FABA to OD-SABA without any regular treatment (NON-REG+OD-SABA). PubMed, the Cochrane library database, and Scopus were searched to identify relevant articles with an outcome measure of the incidence of asthma control. A network meta-analysis was performed and the summary effect size was expressed as the mean difference (MD) with 95% confidence intervals (CIs). The probability of being the best treatment for the outcome and the surface under the cumulative ranking curves were also calculated. Three randomized controlled trials of treatment for mild asthma met the criteria and were included in the study. Non-inferiority of NON-REG+OD-ICS/FABA to REG-ICS+OD-SABA (MD, -0.17; 95% CI, -0.41 to 0.07) and superiority of NON-REG+OD-ICS/FABA to NON-REG+OD-SABA (MD, -0.29; 95% CI, -0.49 to -0.08) were shown in patients with mild asthma. The respective probabilities of being the best treatment for asthma control were 91.2%, 8.8% and 0.2% for NON-REG+OD-ICS/FABA, REG-ICS+OD-SABA, and NON-REG+OD-SABA, respectively, and the surface under the cumulative ranking curves were 1.0, 0.5, and 0.1, respectively. These results suggest that NON-REG+OD-ICS/FABA is an effective alternative to REG-ICS+OD-SABA for asthma control in patients with mild asthma

On-demand Inhaled Corticosteroid and Fast-onset Beta-2 Agonist Combination Therapy Versus Conventional Treatment for Mild to Moderate Asthma: A Non-inferiority, Network Meta-analysis

The aim of this study was to assess the non-inferiority of on-demand (OD) inhaled corticosteroid (ICS) and fast-onset beta-2 agonist (FOBA) combination therapy. Although the guidelines recommend regular inhalation of ICS and long-acting beta-2 agonist (LABA), we investigated whether OD-ICS/FOBA is as effective as regular inhalation. A network meta-analysis of randomized controlled trials was conducted to inspect the non-inferiority of OD-ICS/FOBA efficacy compared with conventional best practice, i.e. regular low – to medium-dose ICS with or without LABA, plus OD short-acting beta-2 agonist (REG-ICS+OD-SABA or REG-ICS/LABA+OD-SABA) in patients with mild to moderate asthma. PubMed, the Cochrane library database, and Scopus were searched to identify relevant articles. Outcome measures were the incidence of asthma exacerbation or aggravation. A network meta-analysis was performed to estimate risk ratios (RRs) with 95% confidence intervals (CIs) and the probability of being the best treatment for the outcome. Four randomized controlled trials of treatment for mild to moderate asthma met the criteria and were included in the study. We could not demonstrate non-inferiority of OD-ICS/FOBA to REG-ICS+OD-SABA (RR, 1.17; 95% CI, 0.61 to 2.26) or to REG-ICS/LABA+OD-SABA (RR, 1.47; 95% CI, 0.79 to 2.71) for mild to moderate asthma. The probability of being the best treatment to reduce asthma exacerbation or aggravation was 10.5% for OD-ICS/FOBA, 10.3% for REG-ICS+OD-SABA, and 79.3% for REG-ICS/LABA+OD-SABA. Surface under the cumulative ranking (SUCRA) curves were 0.4, 0.2 and 0.9 for OD-ICS/FOBA, REG-ICS+OD-SABA, and REG-ICS/LABA+OD-SABA, respectively. Although non-inferiority of OD-ICS/FOBA to conventional best practice was not shown, SUCRA was higher for OD-ICS/FOBA than for REG-ICS+OD-SABA. From these results, we propose that OD-ICS/FOBA can be an effective alternative to REG-ICS+OD-SABA to reduce asthma exacerbation or aggravation in patients with mild to moderate asthma